Table 1. Unclassified variants in BRCA1 and BRCA2.

Exon/intron	Nucleotide change	Amino-acid change	BIC	No. of families	Type of family	Polarity change	Conserved in dog/mouse/rat/chicken	Pathogenic status
BRCA1
2	IVS2–14C>T	Noncoding	Y	1	F, brca only	/	/	UV/P (no aberrant transcript observed by cDNA analysis) Claes et al (2003)
10	IVS10+8C>T	Noncoding	N	1	Sporadic	/	/	UV/P (no aberrant transcript observed by cDNA analysis)
11	2196G>A	D693N	Y	3	F, brca-onlya F, brovca; H, brca only	N (negatively charged → uncharged polar)	N/N/N/N	UV/P (in two of the families true pathogenic BRCA2 mutations (IVS6+1G>A, 1617–1618delAG) were segregating)
11	3238G>A	S1040N	Y	3	H, brca-onlya F, brovca; F, brca only	n	N/Y/Y/N	UV/P [in two of the families pathogenic mutations were segregating (BRCA1 E1221X, BRCA2 1617–618delAG)]
11	3298A>C	E1060A	Y	5	Sporadica F, brca-only; F, brovca H, brca only	N (negatively charged → positively charged)	Y/Y/Y/N	UV/P (variant in linkage disequilibrium with BRCA1 E1221X)
11b	4145A>C	S1342S	N	1	H, brca only	/	/	UV
17	5112G>A	V1665M	Y	1	H, brca only	N	Y/Y/Y/Y	UV/P (not segregating with the disease)
BRCA2
3	407A>G	N60S	Y	1	F, brca only	N	Y/N/N/N	UV
4	IVS4+33A>G	Noncoding	N	1	F, brovca	/	/	UV/P (patient is carrying a pathogenic mutation (BRCA1 Q1281X); no aberrant transcript observed by cDNA analysis)
10	1022–5insT	Noncoding	N	1	H, brovca	/	/	UV/P (no aberrant transcript observed by cDNA analysis) Claes et al (2003)
10b	1441G>A	G405R	N	1	H, brca only	Y	Y/N/Y/N	UV
10	1571G>A	R448H	Y	1	F, brca only	N	N/N/N/N	UV
10	1613A>G	E462G	Y	1	F, brca only	Y	Y/Y/Y/Y	UV
11	3199A>G	N991D	Y	2	H, brca-only F, brovca	Y	N/N/N/N	UV/P (in one of the families BRCA1 5382insC was segregating and the patient was homozygous for N991D)
11	7052A>G	E2275G	N	1	F, brca only, male brca	Y	Y/N/N/Y	UV/P (variant cosegregating with BRCA2 9132delC in one of the families)
14	7285G>C	G2353R	Y	1	F, brovca	Y	Y/N/N/N	UV
14	7641A>G	T2471T	N	1	H, brca only	/	/	UV (identified in two sisters with brca)
15	7691G>A	R2488K	Y	2	H, brca only	N	Y/Y/Y/Y	UV/P (in one family not segregating with the disease; variant in linkage disequilibrium with 2166C>T (S646S))
15	7830G>C	A2534A	N	1	Sporadic	/	/	UV/P
17	8172C>T	S2648S	N	1	Sporadic	/	/	UV/P
18	8395C>G	D2723H	Y	1	H, brca only	N (negatively charged → positively charged)	Y/Y/Y/Y	UV
18	8471G>A	G2748D	Y	1	F, brca only;	Y	Y/Y/Y/Y	UV
20	8795A>C	E2856A	Y	3	F, brca-only; H, brca-only sporadic	Y	Y/Y/Y/Y	UV (not segregating with the disease in one of the families)
22	9078G>T	K2950N	Y	1	F, brca only	N (positively charged → uncharged polar)	Y/Y/Y/Y	UV (identified in two sisters with brca, one of them carrying a truncating BRCA1 mutation)
23	9266C>T	T3013I	Y	1	F, brca only	Y	N/N/N/Y	UV
25	9520T>C	Y3098H	Y	1	F, brca only	N (positively charged → uncharged polar)	N/N/N/Y	UV
25	IVS25+9A>C	Noncoding	Y	1	H, brovca	/	/	UV/P (identified in patient carrying a BRCA1 mutation; no aberrant transcript observed at cDNA level) Claes et al (2003)
27	10338G>A	R3370R	Y	1	H, brca only	/	/	UV/P (identified in a patient carrying BRCA2 Y42C)
27	10462A>G	I3412V	Y	1	F, brca only	N	N/N/N/N	UV/P (not segregating with the disease in the family)

H=hereditary breast cancer; F=familial breast cancer; brca=breast cancer; ovca=ovarian cancer; Brca-only=site-specific breast cancer family; brovca=breast cancer family with at least one case of ovarian cancer; UV=unclassified variant; P=polymorphism; Y=yes; N=no.

^aIn this family two UVs were identified (BRCA1 S1040N and D693N) and one pathogenic mutation (BRCA2 1617–1618delAG).

^bTwo genetic variants identified in the same patient.